Light‐dependent Oxygen Consumption in Bacteriochlorophyll‐Serine‐treated Melanoma Tumors: On‐line Determination Using a Tissue‐inserted Oxygen Microsensor

Abstract

Successful application of anticancer therapy, and especially photodynamic therapy (PDT) mediated by type I1 (PDTII) processes, depends on the oxygen content within the tumor before, during and after treatment. The high consumption of oxygen during type I1 PDT imposes constraints on therapy strategies. Although rates of oxygen consumption and repletion during PDTII were suggested by theoretical studies, direct measurements have not been reported. Application of a novel oxygen sensor allowed continuous and direct in sifu measurements (up to a depth of 8-9 mm from the tumor surface and for several hours) of temporal variations in the oxygen partial pressure (pOz) during PDT. Highly pigmented M2R mouse melanoma tumors implanted in CD1 nude mice were treated with bacteriochlorophyll+erine (Bchl-Ser; a new photodynamic reagent) and were subjected to fractionated illumination (700 < A < 900 nm) at a fluence rate of 12 mW cm+. This illumination led to total oxygen depletion with an average consumption rate of 7.2 pM(Oz) s-l. Spontaneous reoxygenation (at an average rate of 2.5 pM(O,)/s) was observed during the following dark period. These rates are in good agreement with theoretical considerations (Foster et al., Radiat. Res. 126, 296,1991 and Henning et al., Radiut. Res. 142,221,1995). The observed patterns of oxygen consumption and recovery during prolonged periods of Iightldark cycles were interpreted in terms of vasculature damage and sensitizer clearance. The presented data support the previously suggested advantages of fractionated illumination for type I1 photodynamic processes.

<title>Fluorescent and photodynamic properties of near-infrared photosensitizer bacteriochlorophyllide-serine</title>

“…It was confirmed results of morphological study (Fig.12) of tumor after PDT, which have shown a strong vascular damages (hemorrhages (A) and thrombosis (B)) as well as expressed necrosis (A,B) and apoptosis (C) of malignant tissue. These results are in a good agreement with the data of J. Zilberstein et al 5,6 .…”

“…The spectra of tumor fluorescence were investigated before and after irradiation in order to estimate the photo-bleaching of Bchl-Ser in vivo. The level of blood oxygenation in tumor vessels was measured during all time of irradiation and continuing for approximately 10 minutes after it was finished using method described by J. Zilberstein et al 6 .…”

“…This PS of a near infrared range was synthesized and investigated earlier [2][3][4][5][6] , however the peculiarities of processes of sensitization as well as photodynamic action of bacteriochloriphyllide-serine need additional investigations.…”

Light Delivery over Extended Time Periods Enhances the Effectiveness of Photodynamic Therapy

“…Such a mechanism has been proven in preclinical and clinical settings (11,17,19,36,37). Of particular relevance to our study is a report by Foster et al (38), which investigated tumor response to various irradiation regimens composed of constant 2-h duration.…”

Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment

“…Based on the findings presented in this study, the therapeutic effectiveness of the Bchl-ser-PDT þ HT treatment is mediated by a rapidly induced vascular stasis, which in turn can lead to the tumour cells being deprived of O 2 and nutrients. In earlier studies in which the effects of Bchl-ser-PDT alone were monitored in tumour tissue, PDT-induced O 2 consumption (Zilberstein et al, 1997) and changes indicative of vascular stasis (Zilberstein et al, 2001) were also found. While vascular damage has frequently been described as a consequence of PDT, it is not a primary target when PDT is applied in the clinical oncology setting, since, as with ionising radiation and some chemotherapy agents, the PDT effect is O 2 -dependent (Höckel and Vaupel, 2001) and thus, O 2 deprivation due to vascular damage may reduce the treatment efficacy.…”